Patients with pathological degrees of anxiety who meet DSM III criteria for agoraphobia with panic attacks or panic or phobic disorders are evaluated using psychological, physiological, and biochemical methodologies. Patients with major affective illness, particularly those with a significant anxiety component, are also eligible for participation in the program. Particular attention is given to the role of the noradrenergic neurotransmitter system as assessed by: 1) measurement of the metabolite MHPG in urine and plasma; 2) adrenergic receptor number and function in platelets; and 3) neuroendocrine and behavioral response to the alpha-2 adrenergic agonist clonidine, and antagonist yohimbine. Research investigating the relationship of noradrenergic function to other neurotransmitter systems and the hypothalamic-pituitary-adrenal axis also has been initiated. Caffeine and nifedipine challenges are administered to assess their behavioral and biochemical effects. Other approaches to understanding the pathophysiology of anxiety and its potential treatment with alprazolam, carbamazepine, chlonidine, imipramine and verapamil will be explored.